ROLE OF PLATELET-DERIVED GROWTH-FACTOR IN WOUND-HEALING - SYNERGISTIC EFFECTS WITH OTHER GROWTH-FACTORS

ROLE OF PLATELET-DERIVED GROWTH-FACTOR IN WOUND-HEALING - SYNERGISTIC EFFECTS WITH OTHER GROWTH-FACTORS
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DOI:
10.1073/pnas.84.21.7696
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发表时间:
1987-11-01
影响因子:
11.1
通讯作者:
ANTONIADES, HN
ANTONIADES, HN
中科院分区:
综合性期刊1区
文献类型:
--
作者:
LYNCH, SE;NIXON, JC;ANTONIADES, HN

文献摘要

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血小板衍生生长因子(PDGF)在体外刺激成纤维细胞和平滑肌细胞的DNA合成和趋化,并刺激成纤维细胞产生胶原、糖胺聚糖和胶原酶。这些体外特性表明,PDGF在体内由血小板输送到损伤部位,可能在伤口修复过程的启动中发挥重要作用。本文的研究表明,在涉及表皮和真皮的伤口部位添加纯PDGF对愈合伤口的形态学或生物化学几乎没有影响。相反,添加部分纯化的PDGF导致新合成的结缔组织和表皮层的宽度显着呈剂量依赖性增加。使用[3H]胸腺嘧啶放射自显影显示在新的结缔组织和上皮层中标记细胞数量增加。此外,添加部分纯化的PDGF导致伤口部位活检中蛋白质和DNA合成速率以及这些成分的总含量显著增加。当胰岛素样生长因子I与纯PDGF联合添加时,也获得了类似的效果。这些因素的组合导致新形成的结缔组织层的宽度比对照增加2.4倍,表皮厚度增加95%。单独使用胰岛素样生长因子I未引起明显的形态学改变。单独使用表皮生长因子或与PDGF联合使用仅导致表皮增厚。这些结果表明,其他因子与PDGF的协同作用在伤口愈合过程的调节中是重要的。
Platelet-derived growth factor (PDGF) in vitro stimulates DNA synthesis and chemotaxis of fibroblasts and smooth muscle cells and stimulates collagen, glycosaminoglycan, and collagenase production by fibroblasts. These in vitro properties suggest that PDGF, delivered by platelets to the site of injury in vivo, may play an important role in the initiation of the wound repair process. Studies presented here show that the addition of pure PDGF to a wound site involving the epidermis and dermis has little effect on the morphology or biochemistry of the healing wound. In contrast, the addition of partially purified PDGF resulted in significant dose-dependent increases in the width of the newly synthesized connective tissue and epidermal layers. Autoradiography using [3H]thymidine revealed increased number of labeled cells in the new connective tissue and epithelial layers. Furthermore, addition of partially purified PDGF resulted in significant increases in the rate of protein and DNA synthesis and the total content of these components in biopsies taken from the wound site. Similar effects were obtained when insulin-like growth factor I was added in combination with pure PDGF. This combination of factors caused a 2.4-fold increase in the width of the newly formed connective tissue layer and a 95% increase in epidermal thickness compared with controls. Insulin-like growth factor I alone caused no significant morphologic changes. Epidermal growth factor alone or in combination with PDGF resulted in a thickening only of the epidermis. These results indicate that the synergistic actions of other factors with PDGF are important in the modulation of the wound healing process.